Carbon capture and storage (CCS) is vital to climate change mitigation, and has application across the economy, in addition to facilitating atmospheric carbon dioxide removal resulting in emissions offsets and net negative emissions. This contribution reviews the state-of-the-art and identifies key challenges which must be overcome in order to pave the way for its large-scale deployment.
Atrial fibrillation (AF) affects over 33 million individuals worldwide1 and has a complex heritability.2 We conducted the largest meta-analysis of genome-wide association studies for AF to date, consisting of over half a million individuals including 65,446 with AF. In total, we identified 97 loci significantly associated with AF including 67 of which were novel in a combined-ancestry analysis, and 3 in a European specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait loci (eQTL) analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF.
Translating CYP2D6 genotype to metabolizer phenotype is not standardized across clinical laboratories offering pharmacogenetic (PGx) testing and PGx clinical practice guidelines, such as the Clinical Pharmacogenetics Implementation Consortium (CPIC) and the Dutch Pharmacogenetics Working Group (DPWG). The genotype to phenotype translation discordance between laboratories and guidelines can cause discordant cytochrome P450 2D6 (CYP2D6) phenotype assignments and, thus lead to inconsistent therapeutic recommendations and confusion among patients and clinicians. A modified‐Delphi method was used to obtain consensus for a uniform system for translating CYP2D6 genotype to phenotype among a panel of international CYP2D6 experts. Experts with diverse involvement in CYP2D6 interpretation (clinicians, researchers, genetic testing laboratorians, and PGx implementers; n = 37) participated in conference calls and surveys. After completion of 7 surveys, a consensus (> 70%) was reached with 82% of the CYP2D6 experts agreeing to the final CYP2D6 genotype to phenotype translation method. Broad adoption of the proposed CYP2D6 genotype to phenotype translation method by guideline developers, such as CPIC and DPWG, and clinical laboratories as well as researchers will result in more consistent interpretation of CYP2D6 genotype.
Life-cycle assessment has been used to investigate the global warming potential (GWP) and fossil-energy requirement of a hypothetical operation in which biodiesel is produced from the freshwater alga Chlorella vulgaris, grown using flue gas from a gas-fired power station as the carbon source. Cultivation using a twostage method was considered, whereby the cells were initially grown to a high concentration of biomass under nitrogen-sufficient conditions, before the supply of nitrogen was discontinued, whereupon the cells accumulated triacylglycerides. Cultivation in typical raceways and air-lift tubular bioreactors was investigated, as well as different methods of downstream processing. Results from this analysis showed that, if the future target for the productivity of lipids from microalgae, such as C. vulgaris, of ∼40 tons ha -1 year -1 could be achieved, cultivation in typical raceways would be significantly more environmentally sustainable than in closed air-lift tubular bioreactors. While biodiesel produced from microalgae cultivated in raceway ponds would have a GWP ∼ 80% lower than fossil-derived diesel (on the basis of the net energy content), if air-lift tubular bioreactors were used, the GWP of the biodiesel would be significantly greater than the energetically equivalent amount of fossil-derived diesel. The GWP and fossil-energy requirement in this operation were found to be particularly sensitive to (i) the yield of oil achieved during cultivation, (ii) the velocity of circulation of the algae in the cultivation facility, (iii) whether the culture media could be recycled or not, and (iv) the concentration of carbon dioxide in the flue gas. These results highlight the crucial importance of using life-cycle assessment to guide the future development of biodiesel from microalgae.
Proton pump inhibitors (PPIs) are widely used for acid suppression in the treatment and prevention of many conditions, including gastroesophageal reflux disease, gastric and duodenal ulcers, erosive esophagitis, Helicobacter pylori infection, and pathological hypersecretory conditions. Most PPIs are metabolized primarily by cytochrome P450 2C19 (CYP2C19) into inactive metabolites, and CYP2C19 genotype has been linked to PPI exposure, efficacy, and adverse effects. We summarize the evidence from the literature and provide therapeutic recommendations for PPI prescribing based on CYP2C19 genotype (updates at http://www.cpicpgx.org). The potential benefits of using CYP2C19 genotype data to guide PPI therapy include (i) identifying patients with genotypes predictive of lower plasma exposure and prescribing them a higher dose that will increase the likelihood of efficacy, and (ii) identifying patients on chronic therapy with genotypes predictive of higher plasma exposure and prescribing them a decreased dose to minimize the risk of toxicity that is associated with long‐term PPI use, particularly at higher plasma concentrations.
CPIC UPDATETable 1 Assignment of predicted CYP2C19 phenotype based on genotype Predicted phenotype Genotype Examples of CYP2C19 diplotypes a CYP2C19 ultrarapid metabolizer An individual carrying two increased function alleles *17/*17 CYP2C19 rapid metabolizer An individual carrying one normal function allele and one increased function allele *1/*17 CYP2C19 normal metabolizer An individual carrying two normal function alleles *1/*1 CYP2C19 likely intermediate metabolizer b An individual carrying one normal function allele and one decreased function allele or one increased function allele and one decreased function allele or two decreased function alleles *1/*9, *9/*17, *9/*9 CYP2C19 intermediate metabolizer An individual carrying one normal function allele and one no function allele or one increased function allele and one no function allele *1/*2, *1/*3, *2/*17, *3/*17 CYP2C19 likely poor metabolizer b An individual carrying one decreased function allele and one no function allele *2/*9, *3/*9 CYP2C19 poor metabolizer An individual carrying two no function alleles *2/*2, *3/*3, *2/*3 Indeterminate metabolizer An individual carrying one or two uncertain function alleles *1/*12, *2/*12, *12/*14 a Please refer to the CYP2C19 Diplotype-Phenotype Table online for a complete list. For allele functions and population-specific allele and phenotype frequencies, please refer to the CYP2C19 Allele Functionality Table and the CYP2C19 Allele Frequency Table online. 8,9 bThere are limited data to characterize the function of decreased function alleles.
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